We performed a retrospective analysis to compare pancreas transplantation with systemic-enteric drainage (SE) or portal-enteric drainage (PE). METHODS: We reviewed 38 consecutive pancreas transplants including 31 simultaneous kidney-pancreas (SKP) and 7 pancreas after kidney (PAK), using either systemic (n = 18) or portal (n = 20) venous drainage. Demographic, clinical, and immunologic variables were similar for both groups. RESULTS: There were no significant differences in patient, kidney, or pancreas allograft survival rates after a mean follow-up of 23 months (range 1-60). The mean length of hospital stay within 3 months was 34 days among the SE group versus 20 days in the PE group (P = ns). The incidences of intraabdominal infection, early relaparotomy, and acute rejection episodes were not different between groups. The blood pressure levels were similar among the SE and PE groups. There was no significant difference in creatinine, or fasting glucose, C-peptide, cholesterol, or triglyceride levels or homeostatic model assessment (HOMA) beta cell, HOMA-S, and HOMA-IR index. HbA1c was lower at 6 and 12 months in the PE group (P amp;lt; .05). Mean prednisone and mycophenolate mofetil doses as well as tacrolimus levels were identical for both groups. CONCLUSION: The results suggested sustained long-term endocrine function in both groups, showing that in the short term, portal venous drainage did not offer major metabolic or immunologic advantages compared with systemic delivery of insulin.